NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage accumulation in human cells
NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage accumulation in human cells
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DOI：
10.1080/15476286.2018.1467180
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Manley, James L.
中科院分区：
文献类型：
--
作者：
Richard, Patricia;Ogami, Koichi;Manley, James L.
RNA解旋酶Mtr 4是一种多功能蛋白质，是几种不同RNA监视复合物的关键组分。在这里，我们描述了一个新的复杂，包含MTR 4，但有一个不同于任何先前描述的角色。我们发现，Mtr 4协会与人类同源的裂变酵母Nrl 1，NRDE-2，定义了一个新的功能Mtr 4在DNA损伤反应途径。我们提供的生化证据表明，Mtr 4和NRDE-2是同一复合物的一部分，并表明这两种蛋白质通过维持低DNA双链断裂水平在DNA损伤反应中发挥作用。重要的是，Mtr 4/NRDE-2复合物的DNA损伤反应功能不依赖于R环的形成。然而，我们表明NRDE-2和Mtr 4可以影响不同基因子集的R环信号，可能调节它们的表达。我们的工作不仅扩展了Mtr 4的广泛功能，而且还阐明了特征较少的人NRDE-2蛋白的重要作用。
The RNA helicase Mtr4 is a versatile protein that is a crucial component of several distinct RNA surveillance complexes. Here we describe a novel complex that contains Mtr4, but has a role distinct from any of those previously described. We found that Mtr4 association with the human homolog of fission yeast Nrl1, NRDE-2, defines a novel function for Mtr4 in the DNA damage response pathway. We provide biochemical evidence that Mtr4 and NRDE-2 are part of the same complex and show that both proteins play a role in the DNA damage response by maintaining low DNA double-strand break levels. Importantly, the DNA damage response function of the Mtr4/NRDE-2 complex does not depend on the formation of R loops. We show however that NRDE-2 and Mtr4 can affect R-loop signals at a subset of distinct genes, possibly regulating their expression. Our work not only expands the wide range of Mtr4 functions, but also elucidates an important role of the less characterized human NRDE-2 protein.